HPTN Bibliographic Record

Mirochnick M, Nielsen-Saines K, Pilotto JH, Pinto J, Veloso VG, Rossi S, Moye J, Bryson Y, Mofenson L, Camarca M, Watts DH; NICHD HPTN 040/PACTG 1043 Protocol Team. Nelfinavir and Lamivudine pharmacokinetics during the first two weeks of life. Pediatr Infect Dis J. 2011, 30: 769-72. PMC3158246
BACKGROUND: There are no previous data describing nelfinavir and lamivudine pharmacokinetics in neonates treated with weight-band dosing regimens. DESIGN: Pharmacokinetic study of nelfinavir and lamivudine pharmacokinetics in infants during the first 2 weeks of life treated with weight-band dosing regimens. METHODS: Intensive 12-hour pharmacokinetic profiles were performed between either days 4-7 or days 10-14 of life in 26 Brazilian infants. RESULTS: Pharmacokinetic data were obtained from 26 infants who received median (range) per kg doses of 58.8 (48.4-79.0) mg/kg for nelfinavir and 2.0 (1.5-3.2) mg/kg for lamivudine. Median nelfinavir 12-hour AUC (AUC0-12) was 25.5 (1.7-183.5) μg*h/mL and median 12-hour concentration (C12h) was 1.09 (<0.04-14.44) μg/mL. AUC0-12 was less than 15 μg*h/mL (the 10% for adults) in 12 infants (46%). Median lamivudine AUC0-12 was 7.8 (2.7-15.6) μg*h/mL and median C12h was 0.23 (<0.04-0.74) μg/mL. CONCLUSIONS: Lamivudine pharmacokinetic parameters observed in this study were consistent with those seen in other studies of neonates. While median nelfinavir AUC and C12h in these neonates were above the exposure targets, interindividual variability in nelfinavir exposure was large and nelfinavir exposure failed to meet the exposure targets in 46% of infants.